Lung adenocarcinoma

Summary

Lung adenocarcinoma (MONDO:0005061) is a disease (an umbrella term covering 11 Mondo subtypes) with 75 cohort genes (393 GWAS associations across 29 studies) and 214 clinical trials. The dominant Reactome pathway is RAF/MAP kinase cascade (14 cohort genes). Molecularly, EGFR S768I OR EGFR G719A OR EGFR L861Q confers sensitivity to Afatinib in Lung Adenocarcinoma (CIViC Level A); 193 further subtype–drug associations are mapped below. Top therapeutic interventions include pemetrexed, erlotinib, and berberine.

At a glance

• Umbrella term: 11 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 393
• ClinVar variants: 145
• Clinical trials: 214
• Precision-medicine evidence (CIViC): 194 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lung adenocarcinoma
Mondo ID	MONDO:0005061
EFO	EFO:0000571
MeSH	C538231
Orphanet	415268
DOID	DOID:3910
NCIT	C3512
SNOMED CT	254626006
UMLS	C0152013
MedGen	57744
Anatomy (UBERON)	UBERON:0002048
Is cancer (heuristic)	no

Also known as: adenocarcinoma of lung · adenocarcinoma of the lung · lung adenocarcinoma · non-small cell lung adenocarcinoma

Data availability: 145 ClinVar variants · 393 GWAS associations (29 studies) · 2,652 cell lines · 77 intOGen driver records.

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › lung adenocarcinoma

Related subtypes (63): epididymal adenocarcinoma, rete testis adenocarcinoma, seminal vesicle adenocarcinoma, ethmoid sinus adenocarcinoma, lacrimal gland adenocarcinoma, papillary adenocarcinoma, fallopian tube adenocarcinoma, bladder adenocarcinoma, ovarian adenocarcinoma, trabecular adenocarcinoma, middle ear adenocarcinoma, bile duct adenocarcinoma, granular cell carcinoma, small intestine adenocarcinoma, urethra adenocarcinoma, villous adenocarcinoma, thymus gland adenocarcinoma, nasal cavity adenocarcinoma, ureter adenocarcinoma, adenocarcinoma in situ, gastroesophageal junction adenocarcinoma, maxillary sinus adenocarcinoma, mucinous adenocarcinoma, acinar cell carcinoma, adenoid cystic carcinoma, breast adenocarcinoma, clear cell adenocarcinoma, colorectal adenocarcinoma, endometrioid adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, prostate adenocarcinoma, renal cell carcinoma, signet ring cell carcinoma, cervical adenocarcinoma, serous adenocarcinoma, endometrium adenocarcinoma, sweat gland carcinoma, cystadenocarcinoma, tubular adenocarcinoma, mesonephric adenocarcinoma, scirrhous adenocarcinoma, pancreatic adenocarcinoma, follicular variant thyroid gland papillary carcinoma, gallbladder adenocarcinoma, hepatoid adenocarcinoma, intestinal type adenocarcinoma, micropapillary serous carcinoma, minor salivary gland adenocarcinoma, poorly differentiated thyroid gland carcinoma, salivary gland basal cell adenocarcinoma, submandibular gland adenocarcinoma, sebaceous adenocarcinoma, hepatocellular carcinoma, parathyroid gland carcinoma, pituitary adenocarcinoma, vaginal adenocarcinoma, Paget disease, diffuse type adenocarcinoma, vulvar adenocarcinoma, thyroid gland adenocarcinoma, gastroesophageal adenocarcinoma, adenoacanthoma

Subtypes (11): lung adenocarcinoma in situ, lung combined type small cell adenocarcinoma, lung adenoid cystic carcinoma, acinar lung adenocarcinoma, lung occult adenocarcinoma, minimally invasive lung adenocarcinoma, papillary lung adenocarcinoma, lung signet ring cell carcinoma, well-differentiated fetal adenocarcinoma of the lung, lung colloid adenocarcinoma, solid adenocarcinoma with mucin production

Genetics & variants

GWAS landscape

393 GWAS associations across 29 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2853677	2e-110	TERT	?	0.26
rs2036527	3e-82	PSMA4 - CHRNA5	A	1.26
rs7705526	4e-65	TERT	A	1.31
rs1051730	2e-51	CHRNA3	T	1.31
rs55781567	2e-50	CHRNA5	?	0.19
rs11200014	8e-35	FGFR2	A
rs36108040	3e-32	TPRG1 - TP63	?	0.14
rs2736100	2e-31	TERT	G	1.42
rs77468143	6e-29	SECISBP2L - COPS2	T	1.17
rs6554758	1e-28	MIR4457 - CLPTM1L	G	0.86
rs12601991	7e-28	HNF1B	T
rs55768116	2e-26	MPZL3	?	0.12
rs11639372	6e-26	CHRNB4	T	1.19
rs11375254	8e-26	TPRG1 - TP63	T	1.18
rs12265047	2e-24	VTI1A	A	0.18
rs11634901	3e-24	SECISBP2L	A	0.86
rs9374662	3e-23	DCBLD1	?	0.11
chr15:78601997	1e-21		A	0.22
rs56113850	3e-21	CYP2A6	T	0.89
rs137884934	6e-20	PIK3CB - ATP5MC1P3	T	0.8
rs13314271	1e-19	TP63	T	1.11
rs12348845	3e-19	RN7SL151P - MTAP	A	0.13
rs682888	6e-19	DTNB	C	0.9
rs7823498	8e-19	NRG1	?	0.09
rs7859886	9e-19	MTAP	A	0.86
rs1715422	3e-18	MPZL3	T	0.89
rs9387479	3e-18	DCBLD1	T	1.11
rs2736098	5e-18	TERT	T	0.2
rs11813268	2e-17	STN1 - SLK	T	1.13
rs268864	4e-17	ACTR2	A	0.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST012201	Qin N	2020	15,581	27,355	Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma.
GCST90455519	Gorman BR	2024	13,292	67,596	Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.
GCST90455522	Gorman BR	2024	13,292	67,596	Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.
GCST90297562	Shi J	2023	11,753	30,562	Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.
GCST90297563	Shi J	2023	11,753	30,562	Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.
GCST004744	McKay JD	2017	11,273	55,483	Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.
GCST90134662	Byun J	2022	9,791	23,173	Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.
GCST008836	Dai J	2019	8,762	13,328	Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.
GCST003326	Wang Z	2016	5,744	4,817	Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.
GCST000506	Landi MT	2009	5,739	5,848	A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	0
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	50
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	38
intergenic_variant	5
synonymous_variant	2
5_prime_UTR_variant	1
unknown	1
splice_donor_5th_base_variant	1
3_prime_UTR_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2853677	5	1287079	G>A,C,T	0.05	intron_variant	TERT	2e-110	Tier 4: intronic/intergenic
rs2036527	15	78559273	G>A,C,T	0.345	intergenic_variant	PSMA4 - CHRNA5	3e-82	Tier 4: intronic/intergenic
rs7705526	5	1285859	C>A,G,T	0.05	intron_variant	TERT	4e-65	Tier 4: intronic/intergenic
rs1051730	15	78601997	G>A,C,T	0.35	synonymous_variant	CHRNA3	2e-51	Tier 4: intronic/intergenic
rs55781567	15	78565644	C>G	0.05	5_prime_UTR_variant	CHRNA5	2e-50	Tier 2: splice/UTR
rs11200014	10	121575416	G>A,T	0.05	intron_variant	FGFR2	8e-35	Tier 4: intronic/intergenic
rs36108040	3	189618055	A>G	0.05	intron_variant	TPRG1 - TP63	3e-32	Tier 4: intronic/intergenic
rs2736100	5	1286401	C>A,G,T	0.387	intron_variant	TERT	2e-31	Tier 4: intronic/intergenic
rs77468143	15	49084427	T>A,C,G	0.238	intergenic_variant	SECISBP2L - COPS2	6e-29	Tier 4: intronic/intergenic
rs6554758	5	1310037	G>A,C	0.391	intergenic_variant	MIR4457 - CLPTM1L	1e-28	Tier 4: intronic/intergenic
rs12601991	17	37741642	T>A,G	0.05	intron_variant	HNF1B	7e-28	Tier 4: intronic/intergenic
rs55768116	11	118237616	C>A,G,T	0.05	intron_variant	MPZL3	2e-26	Tier 4: intronic/intergenic
rs11639372	15	78674313	C>T	0.404	intron_variant	CHRNB4	6e-26	Tier 4: intronic/intergenic
rs11375254	3	189625454	TAAA>T,TAA,TAAAA,TAAAAA,TAAAAAA	0.05	intron_variant	TPRG1 - TP63	8e-26	Tier 4: intronic/intergenic
rs12265047	10	112728166	G>A,C,T	0.05	intron_variant	VTI1A	2e-24	Tier 4: intronic/intergenic
rs11634901	15	49043021	C>A,T	0.262	intron_variant	SECISBP2L	3e-24	Tier 4: intronic/intergenic
rs9374662	6	117456641	G>A	0.05	intron_variant	DCBLD1	3e-23	Tier 4: intronic/intergenic
chr15:78601997				0.33			1e-21	Tier 4: intronic/intergenic
rs56113850	19	40847202	T>C	0.452	intron_variant	CYP2A6	3e-21	Tier 4: intronic/intergenic
rs137884934	3	138851169	C>T	0.09	intergenic_variant	PIK3CB - ATP5MC1P3	6e-20	Tier 4: intronic/intergenic
rs13314271	3	189639813	T>C	0.476	intron_variant	TP63	1e-19	Tier 4: intronic/intergenic
rs12348845	9	21775493	G>A	0.05	intron_variant	RN7SL151P - MTAP	3e-19	Tier 4: intronic/intergenic
rs682888	2	25534840	T>C	0.47	intron_variant	DTNB	6e-19	Tier 4: intronic/intergenic
rs7823498	8	32546055	C>T	0.05	intron_variant	NRG1	8e-19	Tier 4: intronic/intergenic
rs7859886	9	21811442	A>G	0.165	intron_variant	MTAP	9e-19	Tier 4: intronic/intergenic
rs1715422	11	118233862	T>C	0.242	intron_variant	MPZL3	3e-18	Tier 4: intronic/intergenic
rs9387479	6	117471449	T>A,C,G	0.481	intron_variant	DCBLD1	3e-18	Tier 4: intronic/intergenic
rs2736098	5	1293971	C>A,G,T	0.279	synonymous_variant	TERT	5e-18	Tier 4: intronic/intergenic
rs11813268	10	103922538	C>T	0.224	intron_variant	STN1 - SLK	2e-17	Tier 4: intronic/intergenic
rs268864	2	65262608	G>A,C,T	0.05	intron_variant	ACTR2	4e-17	Tier 4: intronic/intergenic

ClinVar germline variants

145 retrieved; paginated sample, class counts are floors:

82 uncertain significance, 18 pathogenic, 14 likely pathogenic, 11 conflicting classifications of pathogenicity, 5 likely pathogenic; drug response, 4 drug response, 4 benign, 4 likely benign, 2 pathogenic/likely pathogenic, 1 uncertain significance; drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
13966	NM_004333.6(BRAF):c.1801A>G (p.Lys601Glu)	BRAF	Pathogenic	criteria provided, single submitter
13967	NM_004333.6(BRAF):c.1397G>T (p.Gly466Val)	BRAF	Pathogenic	no assertion criteria provided
13968	NM_004333.6(BRAF):c.1790T>G (p.Leu597Arg)	BRAF	Pathogenic	no assertion criteria provided
177620	NM_005228.5(EGFR):c.2236_2250del (p.Glu746_Ala750del)	EGFR	Pathogenic	criteria provided, single submitter
45279	NM_005228.5(EGFR):c.2500G>T (p.Val834Leu)	EGFR	Pathogenic	criteria provided, single submitter
13876	NM_004448.4(ERBB2):c.2328_2336dup (p.Val777_Ser779dup)	ERBB2	Pathogenic	no assertion criteria provided
13877	NM_004448.4(ERBB2):c.2263_2264delinsCC (p.Leu755Pro)	ERBB2	Pathogenic/Likely pathogenic	no assertion criteria provided
431024	NM_004448.4(ERBB2):c.2606T>G (p.Leu869Arg)	ERBB2	Pathogenic	no assertion criteria provided
44992	NM_004448.4(ERBB2):c.2331_2339dup (p.Gly778_Pro780dup)	ERBB2	Pathogenic	criteria provided, single submitter
2431095	NM_004465.2(FGF10):c.*1093A>G	FGF10	Pathogenic	criteria provided, single submitter
7049	NM_013988.2(PARK2):c.(8_8)_(171_171)+180544del	PACRG	Pathogenic	no assertion criteria provided
2174566	NM_004562.3(PRKN):c.601_602insA (p.Cys201Ter)	PRKN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431094	NM_000321.3(RB1):c.380+2T>C	RB1	Pathogenic	criteria provided, single submitter
2431087	NM_001378902.1(ROS1):c.3388G>A (p.Gly1130Arg)	ROS1	Pathogenic	criteria provided, single submitter
376139	NM_001378902.1(ROS1):c.6076G>A (p.Gly2026Arg)	ROS1	Pathogenic	no assertion criteria provided
12366	NM_000546.6(TP53):c.818G>A (p.Arg273His)	TP53	Pathogenic	reviewed by expert panel
142144	NM_000546.6(TP53):c.916C>T (p.Arg306Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
216077	NM_000546.6(TP53):c.584T>C (p.Ile195Thr)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
2431091	NM_000546.6(TP53):c.1051A>T (p.Lys351Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
954591	NM_000546.6(TP53):c.796G>T (p.Gly266Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
431023	t(8;10)(q12.1;q23.31)	ACTA2	Likely pathogenic	no assertion criteria provided
177776	NM_004333.6(BRAF):c.1742A>G (p.Asn581Ser)	BRAF	Likely pathogenic	criteria provided, single submitter
44813	NM_004333.6(BRAF):c.1780G>A (p.Asp594Asn)	BRAF	Likely pathogenic	criteria provided, single submitter
431025	NM_016507.4(CDK12):c.2636G>T (p.Gly879Val)	CDK12	Likely pathogenic	no assertion criteria provided
163380	NM_005228.5(EGFR):c.2582T>A (p.Leu861Gln)	EGFR	Likely pathogenic; drug response	no assertion criteria provided
16608	NM_005228.5(EGFR):c.2240_2257del (p.Leu747_Pro753delinsSer)	EGFR	Likely pathogenic; drug response	no assertion criteria provided
177647	NM_005228.5(EGFR):c.2239_2256del (p.Leu747_Ser752del)	EGFR	Likely pathogenic; drug response	no assertion criteria provided
177649	NM_005228.5(EGFR):c.2240_2254del (p.Leu747_Thr751del)	EGFR	Likely pathogenic; drug response	no assertion criteria provided
177652	NM_005228.5(EGFR):c.2237_2255delinsT (p.Glu746_Ser752delinsVal)	EGFR	Likely pathogenic; drug response	no assertion criteria provided
2583126	NM_005228.5(EGFR):c.709_710delinsTT (p.Ala237Phe)	EGFR	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 198 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 5

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
ROS1	ROS1	GWAS, Orphanet
CHRNA3	CHRNA3	GWAS
CHRNA5	CHRNA5	GWAS
CHRNB4	CHRNB4	GWAS
FOXP4	FOXP4	GWAS

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROS1	Orphanet:251579	Giant cell glioblastoma
ROS1	Orphanet:70567	Cholangiocarcinoma
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
NKX2-1	Orphanet:1429	Benign hereditary chorea
NKX2-1	Orphanet:146	Differentiated thyroid carcinoma
NKX2-1	Orphanet:209905	Brain-lung-thyroid syndrome
NKX2-1	Orphanet:95713	Athyreosis
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	34
gwas_and_clinvar	4
civic_only	18
multi_evidence	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROS1	HGNC:10261	ENSG00000047936	P08922	Proto-oncogene tyrosine-protein kinase ROS	gwas,clinvar,civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar,civic_evidence
NKX2-1	HGNC:11825	ENSG00000136352	P43699	Homeobox protein Nkx-2.1	clinvar,civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
CHRNA3	HGNC:1957	ENSG00000080644	P32297	Neuronal acetylcholine receptor subunit alpha-3	gwas,clinvar
CHRNA5	HGNC:1959	ENSG00000169684	P30532	Neuronal acetylcholine receptor subunit alpha-5	gwas,clinvar
CHRNB4	HGNC:1964	ENSG00000117971	P30926	Neuronal acetylcholine receptor subunit beta-4	gwas,clinvar
FOXP4	HGNC:20842	ENSG00000137166	Q8IVH2	Forkhead box protein P4	gwas,clinvar
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	clinvar,civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	clinvar,civic_evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	clinvar,civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar,civic_evidence
LRP1B	HGNC:6693	ENSG00000168702	Q9NZR2	Low-density lipoprotein receptor-related protein 1B	gwas,civic_evidence
RIT1	HGNC:10023	ENSG00000143622	Q92963	GTP-binding protein Rit1	civic_evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	civic_evidence
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	civic_evidence
TYMS	HGNC:12441	ENSG00000176890	P04818	Thymidylate synthase	civic_evidence
ACTA1	HGNC:129	ENSG00000143632	P68133	Actin, alpha skeletal muscle	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
RICTOR	HGNC:28611	ENSG00000164327	Q6R327	Rapamycin-insensitive companion of mTOR	civic_evidence
EREG	HGNC:3443	ENSG00000124882	O14944	Proepiregulin	civic_evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence
AKT2	HGNC:392	ENSG00000105221	P31751	RAC-beta serine/threonine-protein kinase	civic_evidence
ABCB1	HGNC:40	ENSG00000085563	P08183	ATP-dependent translocase ABCB1	civic_evidence
GATA2	HGNC:4171	ENSG00000179348	P23769	Endothelial transcription factor GATA-2	civic_evidence
MAP2K1	HGNC:6840	ENSG00000169032	Q02750	Dual specificity mitogen-activated protein kinase kinase 1	civic_evidence
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	civic_evidence
ABL2	HGNC:77	ENSG00000143322	P42684	Tyrosine-protein kinase ABL2	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
POLD1	HGNC:9175	ENSG00000062822	P28340	DNA polymerase delta catalytic subunit	civic_evidence
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	civic_evidence
ROBO2	HGNC:10250	ENSG00000185008	Q9HCK4	Roundabout homolog 2	gwas
SATB1	HGNC:10541	ENSG00000182568	Q01826	DNA-binding protein SATB1	gwas
SLC12A7	HGNC:10915	ENSG00000113504	Q9Y666	Solute carrier family 12 member 7	gwas
SLC67A1	HGNC:10964	ENSG00000110628	Q96BI1	Solute carrier family 67 member A1	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gwas
SLK	HGNC:11088	ENSG00000065613	Q9H2G2	STE20-like serine/threonine-protein kinase	gwas
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	gwas
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
SYNGR2	HGNC:11499	ENSG00000108639	O43760	Synaptogyrin-2	gwas
TBK1	HGNC:11584	ENSG00000183735	Q9UHD2	Serine/threonine-protein kinase TBK1	gwas
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TFPI	HGNC:11760	ENSG00000003436	P10646	Tissue factor pathway inhibitor	gwas
TGFB2	HGNC:11768	ENSG00000092969	P61812	Transforming growth factor beta-2 proprotein	clinvar
TLE1	HGNC:11837	ENSG00000196781	Q04724	Transducin-like enhancer protein 1	gwas
TLE3	HGNC:11839	ENSG00000140332	Q04726	Transducin-like enhancer protein 3	gwas
TLR4	HGNC:11850	ENSG00000136869	O00206	Toll-like receptor 4	clinvar
TRPC6	HGNC:12338	ENSG00000137672	Q9Y210	Short transient receptor potential channel 6	gwas
TUB	HGNC:12406	ENSG00000166402	P50607	Tubby protein homolog	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROS1	Proto-oncogene tyrosine-protein kinase ROS	Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
NKX2-1	Homeobox protein Nkx-2.1	Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CHRNA3	Neuronal acetylcholine receptor subunit alpha-3	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
CHRNA5	Neuronal acetylcholine receptor subunit alpha-5	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
CHRNB4	Neuronal acetylcholine receptor subunit beta-4	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
FOXP4	Forkhead box protein P4	Transcriptional repressor that represses lung-specific expression.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
LRP1B	Low-density lipoprotein receptor-related protein 1B	Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis.
RIT1	GTP-binding protein Rit1	Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
TYMS	Thymidylate synthase	Catalyzes the reductive methylation of 2’-deoxyuridine 5’-monophosphate (dUMP) to thymidine 5’-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to…
ACTA1	Actin, alpha skeletal muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
RICTOR	Rapamycin-insensitive companion of mTOR	Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output.
EREG	Proepiregulin	Ligand of the EGF receptor/EGFR and ERBB4.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
AKT2	RAC-beta serine/threonine-protein kinase	Serine/threonine kinase closely related to AKT1 and AKT3.
ABCB1	ATP-dependent translocase ABCB1	Translocates drugs and phospholipids across the membrane.
GATA2	Endothelial transcription factor GATA-2	Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells.
MAP2K1	Dual specificity mitogen-activated protein kinase kinase 1	Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway.
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
ABL2	Tyrosine-protein kinase ABL2	Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endo…
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
POLD1	DNA polymerase delta catalytic subunit	As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair.
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…
ROBO2	Roundabout homolog 2	Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neu…
SATB1	DNA-binding protein SATB1	Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma.
SLC12A7	Solute carrier family 12 member 7	Mediates electroneutral potassium-chloride cotransport when activated by cell swelling.
SLC67A1	Solute carrier family 67 member A1	May act as a transporter of organic cations based on a proton efflux antiport mechanism.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SLK	STE20-like serine/threonine-protein kinase	Mediates apoptosis and actin stress fiber dissolution.
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
SYNGR2	Synaptogyrin-2	May play a role in regulated exocytosis.
TBK1	Serine/threonine-protein kinase TBK1	Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents.
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3’.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TFPI	Tissue factor pathway inhibitor	Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex.
TGFB2	Transforming growth factor beta-2 proprotein	Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
TLE1	Transducin-like enhancer protein 1	Transcriptional corepressor that binds to a number of transcription factors.
TLE3	Transducin-like enhancer protein 3	Transcriptional coregulator that binds to a number of transcription factors.
TLR4	Toll-like receptor 4	Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways.
TRPC6	Short transient receptor potential channel 6	Forms a receptor-activated non-selective calcium permeant cation channel.
TUB	Tubby protein homolog	Functions in signal transduction from heterotrimeric G protein-coupled receptors.

Protein-family classification

Druggable: 23 · Difficult: 20 · Unknown: 32 · Druggable fraction: 0.31

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	14	5.2×	4e-06
Transcription factor	18	2.0×	0.014
Transporter	2	2.1×	0.753
Ion channel	1	1.5×	0.885
Antibody/Immunoglobulin	3	1.2×	0.885
Other/Unknown	32	0.8×	0.992
Scaffold/PPI	2	0.5×	0.992
Enzyme (other)	2	0.3×	0.992
GPCR	1	0.3×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROS1	Kinase	yes	2.7.10.1	LDLR_classB_rpt, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
NKX2-1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CHRNA3	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
CHRNA5	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
CHRNB4	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
FOXP4	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
LRP1B	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
RIT1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TYMS	Enzyme (other)	yes	2.1.1.45	Thymidylate_synthase, Thymidylate_synthase_AS, Thymidate_synth/dCMP_Mease_dom
ACTA1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
RICTOR	Other/Unknown	no		ARM-type_fold, Pianissimo_N, Pianissimo_fam
EREG	Other/Unknown	no		EGF
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
AKT2	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
ABCB1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
GATA2	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3
MAP2K1	Kinase	yes	2.7.12.2	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD
ABL2	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
POLD1	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B_multi_dom, DNA-dir_DNA_pol_B
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom
ROBO2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SATB1	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
SLC12A7	Other/Unknown	no		KCL_cotranspt, AA-permease/SLC12A_dom, SLC12A_fam
SLC67A1	Transporter	yes		Tet-R_TetA/multi-R_MdtG-like, MFS, MFS_dom
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SLK	Kinase	yes		Prot_kinase_dom, UVR_dom, Ser/Thr_kinase_AS
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
SYNGR2	Other/Unknown	no		Marvel, Synaptogyrin
TBK1	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TFPI	Other/Unknown	no		Kunitz_BPTI, TFPI-like, Prtase_inh_Kunz-CS
TGFB2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGFb2
TLE1	Scaffold/PPI	no		WD40_rpt, Groucho/TLE_N, Groucho_enhance
TLE3	Scaffold/PPI	no		WD40_rpt, Groucho/TLE_N, Groucho_enhance
TLR4	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TRPC6	Ion channel	yes		Ankyrin_rpt, TRPC_channel, TRPC6_channel
TUB	Other/Unknown	no		Tubby_C, Tubby_N, Tubby_C_CS

Expression context

Cohort genes with no expression data: 0.

70 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	11
calcaneal tendon	8
primordial germ cell in gonad	7
sural nerve	7
buccal mucosa cell	6
ganglionic eminence	6
male germ line stem cell (sensu Vertebrata) in testis	5
monocyte	5
right lung	5
mucosa of transverse colon	5
cortical plate	4
leukocyte	4
mononuclear cell	4
colonic epithelium	3
right testis	3
sperm	3
skeletal muscle tissue of biceps brachii	3
amniotic fluid	3
upper leg skin	3
secondary oocyte	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROS1	79	tissue_specific	marker	upper lobe of left lung, upper lobe of lung, corpus epididymis
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
NKX2-1	101	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CHRNA3	179	broad	marker	pigmented layer of retina, thymus, primordial germ cell in gonad
CHRNA5	172	ubiquitous	yes	ventricular zone, ganglionic eminence, primordial germ cell in gonad
CHRNB4	125	broad	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, right testis
FOXP4	235	ubiquitous	marker	kidney epithelium, pylorus, body of stomach
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
LRP1B	194	broad	marker	endothelial cell, Brodmann (1909) area 23, cortical plate
RIT1	268	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
TYMS	262	ubiquitous	marker	ventricular zone, embryo, trabecular bone tissue
ACTA1	203	broad	marker	gluteal muscle, skeletal muscle tissue of biceps brachii, diaphragm
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
RICTOR	263	ubiquitous	marker	kidney epithelium, corpus callosum, tibialis anterior
EREG	174	broad	marker	buccal mucosa cell, amniotic fluid, upper leg skin
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
AKT2	272	ubiquitous	marker	right uterine tube, right hemisphere of cerebellum, right lobe of thyroid gland
ABCB1	232	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
GATA2	273	ubiquitous	marker	seminal vesicle, right lung, left uterine tube
MAP2K1	298	ubiquitous	marker	secondary oocyte, oocyte, orbitofrontal cortex
KMT2D	272	ubiquitous	marker	buccal mucosa cell, medial globus pallidus, sural nerve
ABL2	258	ubiquitous	marker	tendon of biceps brachii, buccal mucosa cell, sural nerve
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
POLD1	134	ubiquitous	marker	mucosa of transverse colon, ventricular zone, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 58.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
KRAS	14,509
ERBB2	9,659
SMARCA4	8,138
BRAF	7,394
TLR4	6,974
MAP2K1	5,944
TERT	5,717
TBK1	5,476

Intra-cohort edges

A	B	Sources
ABL2	EGFR	intact
ADGRG6	APOM	intact
AKT2	PIK3CA	string_interaction
AKT2	RICTOR	string_interaction
ALK	KRAS	string_interaction
ALK	RET	intact
BRAF	BRCA2	biogrid_interaction
BRAF	EGFR	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MAP2K1	biogrid_interaction, intact, string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	ROS1	intact
BRAF	TP53	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
CAPZB	DCTN4	biogrid_interaction, intact, string_interaction
CHRNA3	CHRNA5	intact, string_interaction
CHRNA3	CHRNB4	string_interaction
CHRNA5	CHRNB4	intact
EGFR	ERBB2	intact, string_interaction
EGFR	EREG	biogrid_interaction, intact, string_interaction
EGFR	PIK3CA	string_interaction
EGFR	RET	intact
ERBB2	EREG	string_interaction
ERBB2	KRAS	string_interaction
ERBB2	PIK3CA	string_interaction
ERBB2	SLK	string_interaction
FGFR3	GATA2	intact
FGFR3	PIK3CA	string_interaction
FOXP2	FOXP4	biogrid_interaction, intact, string_interaction
FOXP2	NKX2-1	string_interaction
FOXP2	ROBO2	string_interaction
KMT2D	LRP1B	string_interaction
KMT2D	TP53	string_interaction
KMT2D	TP63	string_interaction
KRAS	MAP2K1	biogrid_interaction, string_interaction
KRAS	PIK3CA	string_interaction
KRAS	RASSF3	string_interaction
KRAS	ROS1	string_interaction
KRAS	STK11	string_interaction
KRAS	TP53	string_interaction
KRAS	TUB	intact
LRP1B	PIK3CA	string_interaction
LRP1B	TP53	string_interaction
MAP2K1	PIK3CA	string_interaction
NKX2-1	SMARCA4	intact
PIK3CA	ROS1	string_interaction
PIK3CA	SLTM	intact
PIK3CA	STK11	string_interaction
PIK3CA	TP63	string_interaction

Structural data

PDB: 59 · AlphaFold-only: 16 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
TP53	P04637	313
PIK3CA	P42336	135
BRAF	P15056	131
MAP2K1	Q02750	94
ALK	Q9UM73	79
ERBB2	P04626	63
TYMS	P04818	61
RET	P07949	34
SMARCA4	P51532	31
TP63	Q9H3D4	26
TBK1	Q9UHD2	25
ABCB1	P08183	24
NLRP3	Q96P20	24
TERT	O14746	23
AKT2	P31751	19
PARVA	Q9NVD7	18
RICTOR	Q6R327	16
FGFR3	P22607	15
TLR4	O00206	15
BRCA2	P51587	14
CD163	Q86VB7	14
KMT2D	O14686	11
TGFB2	P61812	11
BAG6	P46379	10
ABL2	P42684	9
TFPI	P10646	9
EREG	O14944	8
SATB1	Q01826	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTA2	P62736	95.43
SLC67A1	Q96BI1	86.91
BTNL2	Q9UIR0	85.97
TLDC2	A0PJX2	85.87
DNAJB4	Q9UDY4	83.43
ATP8B4	Q8TF62	82.12
CHRNA5	P30532	82.04
SYNGR2	O43760	81.52
RASSF3	Q86WH2	79.66
ZFP3	Q96NJ6	75.03
ZNF184	Q99676	72.56
TLE3	Q04726	68.65
ADAMTSL3	P82987	65.99
ALX1	Q15699	61.32
SLTM	Q9NWH9	52.38
LRP1B	Q9NZR2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 922. Enrichment computed across 206 evidence-associated genes (142 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 142 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAF/MAP kinase cascade	14	6.0×	7e-05	BRAF, EGFR, ERBB2, KRAS, SPRED2, EREG, FGF10, FGF7 (+6 more)
PI3K events in ERBB2 signaling	5	23.6×	2e-04	EGFR, ERBB2, EREG, NRG1, PIK3CA
GRB2 events in ERBB2 signaling	5	22.3×	2e-04	EGFR, ERBB2, KRAS, EREG, NRG1
Signaling by ERBB2 KD Mutants	6	17.9×	2e-04	EGFR, ERBB2, KRAS, EREG, NRG1, PIK3CA
Downregulation of ERBB2 signaling	6	16.1×	2e-04	EGFR, ERBB2, EREG, AKT1, AKT2, NRG1
Deactivation of the beta-catenin transactivating complex	7	11.5×	2e-04	SOX9, TLE1, TLE3, AKT1, AKT2, APC, KMT2D
Constitutive Signaling by Aberrant PI3K in Cancer	9	8.0×	2e-04	EGFR, ERBB2, EREG, FGF10, FGF7, FGFR2, FGFR3, NRG1 (+1 more)
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	10	6.8×	2e-04	EGFR, ERBB2, EREG, FGF10, FGF7, FGFR2, FGFR3, AKT1 (+2 more)
PIP3 activates AKT signaling	12	5.6×	2e-04	EGFR, ERBB2, RICTOR, EREG, FGF10, FGF7, FGFR2, FGFR3 (+4 more)
Signaling by ERBB2	6	14.6×	2e-04	EGFR, ERBB2, EREG, AKT1, AKT2, NRG1
FLT3 Signaling	6	14.6×	2e-04	KRAS, SH2B3, AKT1, AKT2, ABL2, PIK3CA
SHC1 events in ERBB2 signaling	5	16.8×	7e-04	EGFR, ERBB2, KRAS, EREG, NRG1
Signaling by ERBB2 TMD/JMD mutants	5	16.8×	7e-04	EGFR, ERBB2, KRAS, EREG, NRG1
PI3K Cascade	6	11.5×	8e-04	FGF10, FGF7, FGFR2, FGFR3, AKT2, PIK3CA
Downregulation of ERBB2:ERBB3 signaling	4	23.0×	0.001	ERBB2, AKT1, AKT2, NRG1
Regulation of TP53 Activity through Association with Co-factors	4	23.0×	0.001	TP53, TP63, AKT1, AKT2
ERBB2 Activates PTK6 Signaling	4	23.0×	0.001	EGFR, ERBB2, EREG, NRG1
ERBB2 Regulates Cell Motility	4	20.1×	0.002	EGFR, ERBB2, EREG, NRG1
Signaling by ERBB2 ECD mutants	4	18.9×	0.002	EGFR, ERBB2, KRAS, PIK3CA
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	4	16.9×	0.004	SOX9, HNF1B, FGF10, FGF7
Regulation of gene expression in early pancreatic precursor cells	3	30.2×	0.004	HNF1B, FGF10, NR5A2
Developmental Lineage of Mammary Gland Myoepithelial Cells	4	15.3×	0.005	EGFR, ERBB2, ACTA2, TP63
Interferon gamma signaling	7	6.2×	0.005	HLA-A, HLA-C, HLA-DPB1, HLA-DQA1, HLA-DRB1, HLA-G, IRF4
Highly calcium permeable nicotinic acetylcholine receptors	3	26.8×	0.006	CHRNA3, CHRNA5, CHRNB4
PI-3K cascade:FGFR2	4	14.0×	0.006	FGF10, FGF7, FGFR2, PIK3CA
Signaling by FGFR2 in disease	5	9.3×	0.006	KRAS, FGF10, FGF7, FGFR2, PIK3CA
SHC-mediated cascade:FGFR2	4	13.4×	0.007	KRAS, FGF10, FGF7, FGFR2
TCF dependent signaling in response to WNT	7	5.8×	0.007	SMARCA4, SOX9, TERT, AKT1, AKT2, APC, KMT2D
FGFR2b ligand binding and activation	3	24.1×	0.007	FGF10, FGF7, FGFR2
Endosomal/Vacuolar pathway	3	21.9×	0.008	HLA-A, HLA-C, HLA-G

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 179 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of gene expression	20	4.3×	8e-05	BRAF, NKX2-1, TP53, KRAS, SOX9, HNF1B, TGFB2, TLE1 (+12 more)
epidermal growth factor receptor signaling pathway	8	11.1×	6e-04	BRAF, EGFR, ERBB2, SOX9, EREG, AKT1, ABL2, PIK3CA
protein autophosphorylation	9	7.3×	0.003	ALK, SLK, STK11, ACVR1B, DDR2, EPHB1, FGFR2, FLT1 (+1 more)
signal transduction	28	2.5×	0.003	CHRNA3, CHRNA5, CHRNB4, EGFR, ERBB2, ALK, RIT1, SOX9 (+20 more)
keratinocyte proliferation	5	16.2×	0.003	TP63, FAM3C, EREG, FGF10, PTCH1
regulation of ERK1 and ERK2 cascade	5	16.2×	0.003	ROS1, ERBB2, NEK10, EPHB1, FGFR2
positive regulation of ERK1 and ERK2 cascade	11	5.2×	0.003	BRAF, EGFR, TLR4, ACTA2, DDR2, FGF10, FGFR2, FGFR3 (+3 more)
ERBB2-ERBB4 signaling pathway	3	47.1×	0.004	ERBB2, EREG, NRG1
ERK1 and ERK2 cascade	6	10.7×	0.004	BRAF, SOX9, TLR4, FAM3C, FGF10, MAP2K1
stem cell proliferation	6	10.5×	0.004	TP53, SOX9, TP63, FGF10, ABCB1, PTCH1
T cell receptor signaling pathway	8	6.8×	0.004	BRAF, STK11, BTNL2, HLA-A, HLA-DPB1, HLA-DRB1, MOG, PIK3CA
positive regulation of transcription by RNA polymerase II	28	2.3×	0.004	NKX2-1, TP53, EGFR, SMARCA4, SOX9, TBK1, TLR4, ALX1 (+20 more)
hair follicle morphogenesis	5	13.8×	0.004	TGFB2, TP63, FGF10, FGF7, FGFR2
embryonic digestive tract morphogenesis	4	20.9×	0.004	HNF1B, FGF10, FGFR2, PITX2
positive regulation of miRNA transcription	6	9.7×	0.004	TP53, EGFR, SMARCA4, TERT, TGFB2, GATA2
negative regulation of neuron apoptotic process	9	5.6×	0.004	BRAF, KRAS, TERT, CLU, EN1, FPR2, PRKN, PIK3CA (+1 more)
positive regulation of epithelial cell proliferation involved in lung morphogenesis	3	40.4×	0.004	FOXP2, FGF7, FGFR2
peptidyl-threonine phosphorylation	4	19.8×	0.004	STK11, TBK1, ACVR1B, AKT1
otic vesicle formation	3	35.3×	0.006	SOX9, FGF10, FGFR2
lacrimal gland development	3	35.3×	0.006	SOX9, FGF10, FGFR2
peptidyl-tyrosine phosphorylation	5	11.8×	0.006	ERBB2, DDR2, FGFR2, FLT1, ABL2
positive regulation of G1/S transition of mitotic cell cycle	5	11.2×	0.007	EGFR, TERT, DDR2, FGF10, AKT1
cell surface receptor protein tyrosine kinase signaling pathway	7	6.8×	0.007	ROS1, ERBB2, ALK, DDR2, FLT1, NRG1, RET
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	2	94.2×	0.007	TP63, FGFR2
mammary gland bud formation	2	94.2×	0.007	FGF10, FGFR2
branch elongation involved in salivary gland morphogenesis	2	94.2×	0.007	FGF10, FGFR2
mesenchymal cell differentiation involved in lung development	2	94.2×	0.007	FGF10, FGFR2
fibroblast growth factor receptor apoptotic signaling pathway	2	94.2×	0.007	FGF10, FGFR3
behavioral response to nicotine	3	31.4×	0.007	CHRNA3, CHRNA5, CHRNB4
positive regulation of epithelial cell proliferation	6	8.2×	0.007	EGFR, ERBB2, SOX9, FGF10, FGF7, FGFR2

Therapeutics

Drugs indicated for this disease

0 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bevacizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Crizotinib	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Ganetespib	Phase 3 (in late-stage trials)
Gefitinib	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Pemetrexed	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Albumin Human, Berberine, Bortezomib, Camrelizumab, Catequentinib, Cetuximab, Durvalumab, Farletuzumab, Firmonertinib, Gemcitabine, Icotinib, Ipilimumab, Lenvatinib, Metformin, Pegfilgrastim, Ponatinib, Poziotinib, Rivoceranib, Serplulimab, Tepotinib, Thymalfasin, Tislelizumab, Vinorelbine, Vintafolide.

Drug target analysis

Approved (phase 4): 25 · Phase ≥3: 25 · Phased (≥1): 30 · Undrugged: 45

Druggability breadth: 88 of 206 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ROS1	LORLATINIB
BRAF	VEMURAFENIB
TP53	NITROFURANTOIN
CHRNA3	VARENICLINE
CHRNA5	VARENICLINE
CHRNB4	VARENICLINE
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
ALK	CERITINIB
KRAS	VEMURAFENIB
STK11	FEDRATINIB
TYMS	FOLIC ACID
SLTM	CABOZANTINIB
FGFR3	PONATINIB
AKT2	CAPIVASERTIB
ABCB1	PROGESTERONE
MAP2K1	VEMURAFENIB
ABL2	BOSUTINIB
PIK3CA	IDELALISIB
RET	PONATINIB
SLK	AFATINIB
TBK1	MOMELOTINIB
TERT	BERBERINE
TLR4	METHOTREXATE
NLRP3	CLOMIPHENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
RET	135	4
ABCB1	119	4
ERBB2	83	4
SLK	81	4
PIK3CA	67	4
FGFR3	64	4
ABL2	63	4
ALK	61	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LORLATINIB	4	ALK, EGFR, ROS1
BRIGATINIB	4	ALK, EGFR, ERBB2, FGFR3, RET, ROS1
REPOTRECTINIB	4	ALK, ROS1
CRIZOTINIB	4	ABL2, ALK, EGFR, FGFR3, PIK3CA, RET
FEDRATINIB	4	ABL2, ALK, BRAF, EGFR, FGFR3, MAP2K1
AXITINIB	4	ABL2, EGFR, FGFR3, MAP2K1, RET, ROS1
ALECTINIB	4	ALK, EGFR, RET, ROS1
INFIGRATINIB PHOSPHATE	4	ALK, BRAF, FGFR3, RET, ROS1
INFIGRATINIB	4	ALK, BRAF, FGFR3, RET, ROS1
ENTRECTINIB	4	ALK, FGFR3, RET, ROS1, SLK, TBK1
CERITINIB	4	ABCB1, ALK, EGFR, FGFR3, RET, ROS1
GILTERITINIB	4	ALK, EGFR, MAP2K1, RET, ROS1, SLK
LAROTRECTINIB	4	ROS1
PAZOPANIB	4	ABL2, ALK, BRAF, FGFR3, RET, ROS1
NINTEDANIB	4	ABCB1, ABL2, ALK, FGFR3, MAP2K1, RET
MITOXANTRONE	4	ABCB1, EGFR, ERBB2, ROS1, TP53
MIDOSTAURIN	4	ABCB1, AKT2, ALK, EGFR, FGFR3, PIK3CA
VEMURAFENIB	4	BRAF, EGFR, KRAS, MAP2K1, RET
PONATINIB	4	ABL2, BRAF, EGFR, ERBB2, FGFR3, RET
SORAFENIB	4	ABL2, BRAF, EGFR, ERBB2, FGFR3, MAP2K1
DASATINIB ANHYDROUS	4	ABL2, BRAF, EGFR, RET
RUXOLITINIB	4	ALK, BRAF, MAP2K1, RET, TBK1
REGORAFENIB	4	BRAF, RET
DABRAFENIB	4	ABL2, BRAF, KRAS
COBIMETINIB	4	BRAF, MAP2K1
NILOTINIB	4	ABL2, BRAF, RET
ABEMACICLIB	4	BRAF, EGFR
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	ABL2, BRAF
DASATINIB	4	ABL2, BRAF, EGFR, ERBB2, FGFR3, MAP2K1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 16.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
ALK	1,815	Binding:1801, Functional:13, ADMET:1
RET	1,586	Binding:1573, Functional:10, ADMET:3
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
MAP2K1	1,200	Binding:1150, Functional:47, ADMET:3
FGFR3	975	Binding:948, Functional:18, ADMET:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
AKT2	822	Binding:802, Functional:19, Toxicity:1
NLRP3	534	Binding:527, Functional:6, ADMET:1
TBK1	475	Binding:473, Functional:2
ROS1	461	Binding:459, Functional:2
CHRNA3	436	Binding:343, Functional:91, ADMET:2
CHRNB4	407	Binding:309, Functional:96, ADMET:2
TERT	391	Binding:389, Functional:2
TYMS	376	Binding:373, ADMET:2, Functional:1
ABL2	358	Binding:356, Functional:1, ADMET:1
SLK	280	Binding:279, Functional:1
TLR4	267	Binding:254, Functional:10, ADMET:3
STK11	244	Binding:244
SMARCA4	230	Binding:207, ADMET:12, Functional:11
TFPI	116	Binding:116
RICTOR	99	Binding:99
TRPC6	30	Binding:30
ACTR2	23	Binding:23
CHRNA5	21	Binding:16, Functional:4, ADMET:1
SLTM	14	Binding:14
KMT2D	11	Binding:11
CAPZB	9	Binding:9
POLD1	8	Binding:8
SOX9	3	Binding:3
TGFB2	3	Binding:3
ADGRG6	2	Binding:2
MYNN	2	Binding:2
GATA2	1	Binding:1
SLC67A1	1	Binding:1
SYNGR2	1	Binding:1
ZFP3	1	Binding:1
BAG6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ROS1	2.7.10.1	receptor protein-tyrosine kinase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
ALK	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
TYMS	2.1.1.45	thymidylate synthase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
AKT2	2.7.11.1	non-specific serine/threonine protein kinase
ABCB1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
MAP2K1	2.7.12.2	mitogen-activated protein kinase kinase
ABL2	2.7.10.2	non-specific protein-tyrosine kinase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
POLD1	2.7.7.7	DNA-directed DNA polymerase
RET	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ROS1	461
BRAF	1,442
TP53	869
CHRNA3	436
CHRNB4	407
EGFR	6,531
ERBB2	1,221
ALK	1,815
KRAS	861
SMARCA4	230
STK11	244
TYMS	376
FGFR3	975
AKT2	822
ABCB1	3,063
MAP2K1	1,200
ABL2	358
PIK3CA	2,034
RET	1,586
SLK	280
TBK1	475
TERT	391
TFPI	116
TLR4	267
NLRP3	534

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

27 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LORLATINIB	4	ALK, EGFR, ROS1
BRIGATINIB	4	ALK, EGFR, ERBB2, FGFR3, RET, ROS1
REPOTRECTINIB	4	ALK, ROS1
FEDRATINIB	4	ABL2, ALK, BRAF, EGFR, FGFR3, MAP2K1
AXITINIB	4	ABL2, EGFR, FGFR3, MAP2K1, RET, ROS1
ALECTINIB	4	ALK, EGFR, RET, ROS1
INFIGRATINIB PHOSPHATE	4	ALK, BRAF, FGFR3, RET, ROS1
INFIGRATINIB	4	ALK, BRAF, FGFR3, RET, ROS1
ENTRECTINIB	4	ALK, FGFR3, RET, ROS1, SLK, TBK1
CERITINIB	4	ABCB1, ALK, EGFR, FGFR3, RET, ROS1
GILTERITINIB	4	ALK, EGFR, MAP2K1, RET, ROS1, SLK
LAROTRECTINIB	4	ROS1
PAZOPANIB	4	ABL2, ALK, BRAF, FGFR3, RET, ROS1
MITOXANTRONE	4	ABCB1, EGFR, ERBB2, ROS1, TP53
MIDOSTAURIN	4	ABCB1, AKT2, ALK, EGFR, FGFR3, PIK3CA
VEMURAFENIB	4	BRAF, EGFR, KRAS, MAP2K1, RET
SORAFENIB	4	ABL2, BRAF, EGFR, ERBB2, FGFR3, MAP2K1
DASATINIB ANHYDROUS	4	ABL2, BRAF, EGFR, RET
RUXOLITINIB	4	ALK, BRAF, MAP2K1, RET, TBK1
REGORAFENIB	4	BRAF, RET
DABRAFENIB	4	ABL2, BRAF, KRAS
COBIMETINIB	4	BRAF, MAP2K1
NILOTINIB	4	ABL2, BRAF, RET
ABEMACICLIB	4	BRAF, EGFR
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	ABL2, BRAF
DASATINIB	4	ABL2, BRAF, EGFR, ERBB2, FGFR3, MAP2K1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	25	ROS1, BRAF, TP53, CHRNA3, CHRNA5, CHRNB4, EGFR, ERBB2, ALK, KRAS (+15 more)
B	Phased (≥1) drug, not yet approved	5	SMARCA4, RICTOR, TGFB2, TRPC6, ACTR2
C	Druggable family + PDB, no drug	2	ROBO2, ADGRG6
D	Druggable family + AlphaFold only, no drug	3	SLC67A1, BTNL2, ADAMTSL3
E	Difficult family or no structure, no drug	40	NKX2-1, FOXP4, LRP1B, RIT1, ACTA1, EREG, GATA2, KMT2D, POLD1, SATB1 (+30 more)

Undrugged target profiles

45 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
EREG	0	EGFR
ZFP3	1	TP53
TFPI	116	—
NKX2-1	0	—
FOXP4	0	—
LRP1B	0	—
RIT1	0	—
ACTA1	0	—
GATA2	1	—
KMT2D	11	—
POLD1	8	—
ROBO2	0	—
SATB1	0	—
SLC12A7	0	—
SLC67A1	1	—
BRCA2	0	—
SOX9	3	—
BTNL2	0	—
SYNGR2	1	—
HNF1B	0	—
TLE1	0	—
TLE3	0	—
TUB	0	—
ZNF184	0	—
ACTA2	0	—
POLR1H	0	—
ATP8B4	0	—
ADGRG6	2	—
FOXP2	0	—
APOM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 214.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	83
PHASE2	65
PHASE1/PHASE2	21
PHASE1	19
PHASE3	18
EARLY_PHASE1	4
PHASE4	2
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00021060	PHASE2/PHASE3	COMPLETED	Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Advanced, Metastatic, or Recurrent Non-Small Cell Lung Cancer
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04929041	PHASE2/PHASE3	SUSPENDED	Testing the Addition of Radiation Therapy to the Usual Treatment (Immunotherapy With or Without Chemotherapy) for Advanced Stage Non-small Cell Lung Cancer Patients Who Are PD-L1 Negative
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT01386385	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT02493582	PHASE2	ACTIVE_NOT_RECRUITING	The Study of Apatinib Plus CIK as the Third Line Therapy for Advanced Lung Adenocarcinoma Patients With Wild-Type EGFR
NCT02864992	PHASE2	ACTIVE_NOT_RECRUITING	Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)
NCT03110978	PHASE2	ACTIVE_NOT_RECRUITING	Stereotactic Body Radiation Therapy With or Without Nivolumab in Treating Patients With Stage I-IIA or Recurrent Non-small Cell Lung Cancer
NCT04105270	PHASE2	RECRUITING	RMT in Combination With Durvalumab + Chemo in Untreated Adenocarcinoma NSCLC. A Randomized Double Blind Phase II Trial
NCT04533451	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Effects of MK-3475 (Pembrolizumab) With or Without the Usual Chemotherapy Treatment for Patients 70 Years of Age and Older With Advanced Non-small Cell Lung Cancer
NCT04557449	PHASE2	ACTIVE_NOT_RECRUITING	Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
NCT04625647	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)
NCT04802876	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients with PD1-high MRNA Expressing Tumors
NCT05198830	PHASE2	RECRUITING	Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer
NCT05266846	PHASE2	RECRUITING	Pembrolizumab Plus Bevacizumab and Chemotherapy for ALK-rearranged NSCLC With Persistent 5’ALK
NCT05456256	PHASE2	RECRUITING	A Study of LP-300 With Carboplatin and Pemetrexed in Never Smokers With Advanced Lung Adenocarcinoma
NCT05503667	PHASE2	RECRUITING	Neoadjuvant Furmonertinib Plus Bevacizumab or Furmonertinib Monotherapy for Resectable and Potentially Resectable Stage III-IVA EGFR Mutation-Positive Lung Adenocarcinoma
NCT05528458	PHASE2	RECRUITING	Osimertinib to Suppress the Progression of Remaining GGN for EGFR Mutation-positive Stage IB-IIIA Lung Adenocarcinoma
NCT05558904	PHASE1/PHASE2	RECRUITING	An Investigational Scan (Me-4FDG PET/CT) for the Detection of Sodium-Glucose Transport for Early Diagnosis of Lung Cancer
NCT05733000	PHASE2	RECRUITING	CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors
NCT05797168	PHASE1/PHASE2	RECRUITING	Phase I/IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PEMETREXED	4	16
ERLOTINIB	4	4
BERBERINE	4	3
CARBOPLATIN	4	3
DOCETAXEL ANHYDROUS	4	3
GEFITINIB	4	3
NINTEDANIB	4	3
PACLITAXEL	4	3
CRIZOTINIB	4	2
IPILIMUMAB	4	2
AFATINIB	4	1
ALBUMIN HUMAN	4	1
ASPIRIN	4	1
AURANOFIN	4	1
BEVACIZUMAB	4	1
CETUXIMAB	4	1
DAPAGLIFLOZIN PROPANEDIOL	4	1
ETOPOSIDE	4	1
NIVOLUMAB	4	1
ORLISTAT	4	1
OSIMERTINIB	4	1
PACRITINIB	4	1
PEGFILGRASTIM	4	1
PENTOSTATIN	4	1
PONATINIB	4	1
RUCAPARIB	4	1
SOTORASIB	4	1
TEPOTINIB	4	1
TISLELIZUMAB	4	1
TRAMETINIB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 194 predictive associations from 235 curated evidence items; also 15 prognostic, 11 oncogenic, 2 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
EGFR S768I OR EGFR G719A OR EGFR L861Q	Afatinib	Sensitivity/Response	CIViC A	EID11229
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC B	EID3782 +3
EGFR Exon 19 Deletion	Afatinib	Sensitivity/Response	CIViC B	EID880 +3
EGFR L858R	Gefitinib	Sensitivity/Response	CIViC B	EID2634 +2
EGFR L858R	Afatinib	Sensitivity/Response	CIViC B	EID879 +2
EGFR Exon 19 Deletion	Gefitinib	Sensitivity/Response	CIViC B	EID2519 +1
EGFR L858R	Erlotinib	Sensitivity/Response	CIViC B	EID4290 +1
EGFR G719	Erlotinib	Sensitivity/Response	CIViC B	EID1780
EGFR L858R OR EGFR Exon 19 Deletion	Erlotinib	Sensitivity/Response	CIViC B	EID3791
EGFR Mutation	EGFR Tyrosine Kinase Inhibitor Therapy + Metformin	Sensitivity/Response	CIViC B	EID12074
KRAS Mutation	Salirasib	Sensitivity/Response	CIViC B	EID1218
LRP1B Loss-of-function	Immune Checkpoint Inhibitor	Sensitivity/Response	CIViC B	EID12652
MET Amplification OR MET Exon 14 Skipping Mutation OR v::ALK Fusion OR v::ROS1 Fusion	Crizotinib	Sensitivity/Response	CIViC B	EID11385
MTAP Underexpression AND CDKN2A Underexpression	Pemetrexed	Sensitivity/Response	CIViC B	EID12723
RET Fusion	Cabozantinib	Sensitivity/Response	CIViC B	EID4847
TMB High	Ipilimumab/Nivolumab Regimen	Sensitivity/Response	CIViC B	EID12614
EGFR Exon 20 Insertion	Erlotinib	Resistance	CIViC B	EID9222 +2
EGFR Exon 20 Insertion	Afatinib	Resistance	CIViC B	EID1809
EGFR T790M	Gefitinib + Erlotinib	Resistance	CIViC B	EID1391
KRAS G12A	Gefitinib + Erlotinib	Resistance	CIViC B	EID251
STK11 Mutation	Nivolumab + Atezolizumab + Pembrolizumab	Resistance	CIViC B	EID6441
TYMS Amplification	Pemetrexed	Resistance	CIViC B	EID903
MET Exon 14 Skipping Mutation	Crizotinib	Sensitivity/Response	CIViC C	EID11384 +8
MET Exon 14 Skipping Mutation	Tepotinib	Sensitivity/Response	CIViC C	EID11464 +3
EGFR E746_A750del	Erlotinib	Sensitivity/Response	CIViC C	EID4205 +2
EGFR::RAD51 Fusion	Erlotinib	Sensitivity/Response	CIViC C	EID11015 +2
MET Amplification	Crizotinib	Sensitivity/Response	CIViC C	EID11383 +2
MET Exon 14 Skipping Mutation AND CD274 Overexpression	Tepotinib	Sensitivity/Response	CIViC C	EID11460 +2
EGFR::RAD51 Fusion	Osimertinib	Sensitivity/Response	CIViC C	EID11021 +1
ERBB2 Y772_A775DUP	Afatinib	Sensitivity/Response	CIViC C	EID1045 +1

+164 more predictive associations (showing top 30 by evidence level).